Is HRAS p.Ser106= (c.318G>A) pathogenic?

HRAS p.Ser106= (c.318G>A) is classified Likely benign in HRAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-06). Very rare (popmax 0.00801%, afr); Associated with Cardiovascular phenotype.

What condition is associated with HRAS p.Ser106= (c.318G>A)?

HRAS p.Ser106= (c.318G>A) is associated with Cardiovascular phenotype, Costello syndrome (ClinVar).

How common is HRAS p.Ser106= (c.318G>A) in the general population?

HRAS p.Ser106= (c.318G>A) is very rare (popmax 0.00801%, afr) (gnomAD).

HRAS p.Ser106=

c.318G>A · rs1053376922 · VCV1114424

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.7
Overall
CADD	1.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,922 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000558% 9/1,613,730 alleles · very rare exomes 7/1,461,550 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,487
East Asian	0.00223%	44,902
European (non-Finnish)	0.000169%	589,998

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: HRAS
Protein: p.Ser106=
Coding: c.318G>A
MANE Select: NM_005343
dbSNP: rs1053376922
Type: single nucleotide variant
Location: chr11:533585 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 256 PDB
Residue 106: a β-strand

Full HRAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Costello syndrome

Similar variants

HRAS p.Ser106Trp Uncertain significance ★★ ⚠ same residue
HRAS p.Ser106Leu Uncertain significance ★ ⚠ same residue
HRAS p.Ala59Thr Likely pathogenic ★★★ same condition
HRAS p.Gly12Ser Pathogenic ★★★ same condition
HRAS p.Gly13Cys Pathogenic ★★★ same condition
HRAS p.Lys117Arg Pathogenic ★★★ same condition
HRAS p.Thr58Ile Pathogenic ★★★ same condition
HRAS p.Gly138Ser Uncertain significance ★★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/hras-p-ser106 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown